HRP20190689T1

HRP20190689T1 - Tear lipocalin muteins binding il-4 r alpha

Info

Publication number: HRP20190689T1
Application number: HRP20190689TT
Authority: HR
Inventors: Andreas Hohlbaum; Alexandra Baehre; Gabriele Matschiner; Stefan Trentmann; Klaus KIRCHFLED; Hans-Juergen Christian
Original assignee: Pieris Pharmaceuticals Gmbh; Astrazeneca Ab
Priority date: 2010-06-08
Filing date: 2019-04-12
Publication date: 2019-06-14
Also published as: US20150283207A1; HUE043835T2; CN105949301B; PL2580236T3; SG186161A1; EP2580236A2; JP2016028604A; AU2011263786A1; US20130085113A1; US9687524B2; JP2013537400A; JP6766194B2; US10232014B2; CA2800026C; SI2580236T1; ZA201209160B; US20190240289A1; DK2580236T3; CN105949301A; US8986951B2

Claims

1. Mutein ljudskog suznog lipokalina, naznačen time što mutein sadrži: (i) slijedeće supstitucije amino kiselina Glu 27 → Arg, Phe 28 → Cys, Glu 30 → Arg, Met 31 → Ala, Leu 33 → Tyr, Ile 57 → Arg, Cys 61 → Trp, Asp 80 → Ser, Lys 83 → Arg, Glu 104 → Leu, Leu 105 → Cys, His 106 → Pro, Lys 108 → Gin; i (ii) jedan od slijedećih skupova aminokiselinskih supstitucija (1) Arg 26 → Pro, Asn 32 → Tyr, Glu 34 → Ser, Met 55 → Ala, Leu 56 → Gin, Glu 63 → Lys; (2) Arg 26 → Ser, Asn 32 → Tyr, Glu 34 → Val, Met 55 → Ala, Leu 56 → Ala, Ser 58 → Ile, Glu 63 → Ser; (3) Arg 26 → Ser, Asn 32 → Val, Glu 34 → Asn, Met 55 → Ala, Leu 56 → Gln, Ser 58 → Lys, Glu 63 → Lys; (4) Arg 26 → Asn, Asn 32 → Lys, Glu 34 → Asp, Met 55 → Ala, Leu 56 → His, Ser 58 → Arg, Glu 63 → Gln; (5) Arg 26 → Tyr, Asn 32 → Tyr, Glu 34 → His, Met 55 → Ala, Leu 56 → His, Ser 58 → Ala, Glu 63 → Lys; (6) Arg 26 → Lys, Asn 32 → Tyr, Glu 34 → Arg, Met 55 → Ala, Leu 56 → Lys, Ser 58 → Asn, Glu 63 → Pro; ili (7) Arg 26 → Glu, Asn 32 → His, Glu 34 → Gly, Met 55 → Ala, Leu 56 → Met, Ser 58 → Leu, Glu 63 → Lys; i (iii) najmanje 75% identičnosti sa sekvencom zrelog ljudskog suznog lipokalina, pri čemu je sekvenca zrelog ljudskog suznog lipokalina i pri čemu se mutein veže na ljudski IL-4 receptor alfa s konstantom disocijacije (KD) od ispod 0.1 nM.1. Mutein of human tear lipocalin, characterized in that the mutein contains: (i) the following amino acid substitutions Glu 27 → Arg, Phe 28 → Cys, Glu 30 → Arg, Met 31 → Ala, Leu 33 → Tyr, Ile 57 → Arg, Cys 61 → Trp, Asp 80 → Ser, Lys 83 → Arg, Glu 104 → Leu, Leu 105 → Cys, His 106 → Pro, Lys 108 → Gin; and (ii) one of the following sets of amino acid substitutions (1) Arg 26 → Pro, Asn 32 → Tyr, Glu 34 → Ser, Met 55 → Ala, Leu 56 → Gin, Glu 63 → Lys; (2) Arg 26 → Ser, Asn 32 → Tyr, Glu 34 → Val, Met 55 → Ala, Leu 56 → Ala, Ser 58 → Ile, Glu 63 → Ser; (3) Arg 26 → Ser, Asn 32 → Val, Glu 34 → Asn, Met 55 → Ala, Leu 56 → Gln, Ser 58 → Lys, Glu 63 → Lys; (4) Arg 26 → Asn, Asn 32 → Lys, Glu 34 → Asp, Met 55 → Ala, Leu 56 → His, Ser 58 → Arg, Glu 63 → Gln; (5) Arg 26 → Tyr, Asn 32 → Tyr, Glu 34 → His, Met 55 → Ala, Leu 56 → His, Ser 58 → Ala, Glu 63 → Lys; (6) Arg 26 → Lys, Asn 32 → Tyr, Glu 34 → Arg, Met 55 → Ala, Leu 56 → Lys, Ser 58 → Asn, Glu 63 → Pro; or (7) Arg 26 → Glu, Asn 32 → His, Glu 34 → Gly, Met 55 → Ala, Leu 56 → Met, Ser 58 → Leu, Glu 63 → Lys; and (iii) at least 75% identity to the sequence of mature human lacrimal lipocalin, wherein the sequence of mature human lacrimal lipocalin and wherein the mutein binds to human IL-4 receptor alpha with a dissociation constant (KD) of less than 0.1 nM.

2. Mutein prema patentnom zahtjevu 1, naznačen time što nadalje sadrži sljedeći skup aminokiselinskih supstitucija: (1) Val 53 → Phe, Val 64 → Tyr, Ala 66 → Leu.2. Mutein according to claim 1, characterized in that it further contains the following set of amino acid substitutions: (1) Val 53 → Phe, Val 64 → Tyr, Ala 66 → Leu.

3. Mutein prema bilo kojem od prethodnih patentnih zahtjeva, naznačen time što su izbrisana prva četiri N-terminalna aminokiselinska ostatka o sekvence zrelog ljudskog suznog lipokalina i/ili posljednja dva C-terminalna aminokiselinska ostatka sekvence zrelog ljudskog suznog lipokalina.3. Mutein according to any of the preceding patent claims, characterized in that the first four N-terminal amino acid residues of the sequence of mature human tear lipocalin and/or the last two C-terminal amino acid residues of the sequence of mature human tear lipocalin are deleted.

4. Mutein prema bilo kojem od prethodnih patentnih zahtjeva, naznačen time što mutein ima aminokiselinsku sekvencu kao što je prikazano u SEQ ID No: 4, i 6-11.4. A mutein according to any one of the preceding claims, characterized in that the mutein has an amino acid sequence as shown in SEQ ID No: 4, and 6-11.

5. Fuzijski protein naznačen time što sadrži mutein prema bilo kojem od zahtjeva 1 do 4.5. A fusion protein characterized in that it contains a mutein according to any one of claims 1 to 4.

6. Molekula nukleinske kiseline naznačena time što sadrži nukleotidnu sekvencu koja kodira mutein prema bilo kojem od zahtjeva 1 do 4 ili fuzijski protein prema zahtjevu 5.6. Nucleic acid molecule characterized by containing a nucleotide sequence encoding a mutein according to any one of claims 1 to 4 or a fusion protein according to claim 5.

7. Stanica domaćin naznačena time što sadrži molekulu nukleinske kiseline prema zahtjevu 6.7. A host cell characterized by the fact that it contains a nucleic acid molecule according to claim 6.

8. Farmaceutski ili dijagnostički pripravak naznačen time što sadrži mutein prema bilo kojem od zahtjeva 1 do 4 ili fuzijski protein prema zahtjevu 5.8. A pharmaceutical or diagnostic preparation characterized in that it contains a mutein according to any one of claims 1 to 4 or a fusion protein according to claim 5.